Impact of commonly used drugs on the composition and metabolic function of the gut microbiota

Abstract

The human gut microbiota has now been associated with drug responses and efficacy, while chemical compounds present in these drugs can also impact the gut bacteria. However, drug-microbe interactions are still understudied in the clinical context, where polypharmacy and comorbidities co-occur. Here, we report relations between commonly used drugs and the gut microbiome. We performed metagenomics sequencing of faecal samples from a population cohort and two gastrointestinal disease cohorts. Differences between users and nonusers were analysed per cohort, followed by a meta-analysis. While 19 of 41 drugs are found to be associated with microbial features, when controlling for the use of multiple medications, proton-pump inhibitors, metformin, antibiotics and laxatives show the strongest associations with the microbiome. We here provide evidence for extensive changes in taxonomy, metabolic potential and resistome in relation to commonly used drugs. This paves the way for future studies and has implications for current microbiome studies by demonstrating the need to correct for multiple drug use.

Proteobacteria Overgrowth and Butyrate-Producing Taxa Depletion in the Gut Microbiota of Glycogen Storage Disease Type 1 Patients

“…Since patients are commonly taking multiple drugs to cope with the variety of comorbidities characterizing glycogen storage diseases, we tried to evaluate their possible impacts on the microbial community. Indeed, multi-drug usage has been reported to impact microbial composition and richness, but it is difficult to assess whether the observed alterations are caused by the high number of drugs or by the disease itself, forcing the patient to take all these medications [47]. Whereas few drugs seem to have a direct effect on the microbiota, i.e., metformin or proton pump inhibitors, the association of multiple compounds is not clearly associated to the depletion or enrichment of specific taxa.…”

Interaction between drugs and the gut microbiome

“…A more recent study further assessed the impact of polypharmacy and comorbidities on the gut microbiome. 19 This study took a more in-depth look by performing a meta-analysis of the associations between drug use and the gut microbiome in three independent cohorts, including patients with inflammatory bowel disease and irritable bowel syndrome, and found 19 of the 41 medication categories studied to be associated with the gut microbiome. As many of the study participants used multiple drugs, a stepwise approach was used to regress out the effect of polypharmacy.…”

“…After statistically correcting for polypharmacy, PPIs, metformin, antibiotics and laxatives still showed significant associations with microbial features. 19 Despite the high consistency of drug-microbe associations detected in multiple human cohorts, differences in the estimated effect sizes reflect differences in drug usage in different European countries and in different patients. For instance, the observed impact of antibiotic use on microbial composition in the Belgium Flemish cohort was higher than that in the Dutch LifeLines-DEEP cohort, which is line with the fact that the prescription rate of antibiotics is higher in Belgium than in the Netherlands.…”

“…A higher dosage also seems to be associated with larger microbial changes. 19 A recent study that used metagenomic sequence data, allowing for both high resolution taxonomy and predicted pathway analysis, studied the effect of 41 commonly used drugs on the gut microbiome and again observed that PPIs accounted for the largest number of associations. 19 After correcting for the impact of concomitant use of other drugs, PPIs were significantly associated with 24 taxa and 133 pathways.…”

“…While several bacterial taxa, including Bifidobacterium and Ruminococcus species, are predicted to contribute to these pathways, statistical analyses showed that only the changes in Streptococcus mutans contributed to the predicted pathway changes due to PPI use. 19 The reduction of gastric acidity induced by PPIs is thought to be responsible for the observed microbial changes since it enables oral bacteria to colonise the gut microbiome, leading to changes in taxonomic homoeostasis (figure 1). This is supported by the observation of an 'oralisation' of the gut microbiome in PPI users.…”